Submitted January 17, 2002
Returned for revision February 6, 2002
Accepted July 8, 2002
Ovary
Inhibin A Increases Apoptosis in Early Ovarian Antral
Follicles of Diethylstilbestrol-Treated Rats
Alejandra M. Vitale 1,
Olga M. Gonzalez 2,
Fernanda Parborell 1,
Griselda Irusta 1,
Stella Campo 3,
Marta Tesone 1*
1 Instituto de Biologia y Medicina Experimental
2 Universidad de Buenos Aires, Facultad de Agronomia
3 Centro de Investigaciones Endocrinológicas
* To whom correspondence should be addressed. E-mail: mtesone{at}dna.uba.ar.
Abstract
The purpose of this study was to evaluate the role of
inhibin A (Inh) in follicular development and apoptosis-
related mechanisms, in preantral and early antral
follicles from prepubertal DES-treated rats. Granulosa
cells isolated from the ovaries of 23- to 25-day-old rats
were cultured in serum- free medium containing FSH (20
ng/ml), TGFß (5 ng/ml), and estradiol (50 ng/ml) in
the presence or absence of different concentrations of
Inh. 3H-thymidine incorporation was decreased
in the presence of Inh, while no significant changes where
observed in culture media on progesterone (P) and
estradiol (E) levels. An increase in low molecular weight
DNA fragmentation indicative of apoptosis, and an increase
in the protein levels of Bax with no changes in Bcl-2,
were evident in early antral follicles incubated 24 h with
Inh. For each animal Inh (0.5 µg/ovary) was injected
intrabursally in one ovary while the contralateral ovary
served as control. Ovarian histology revealed an
inhibitory effect of Inh treatment on the follicular
development induced by DES. At 24 h of Inh injection, the
number of preantral follicles was increased as compared to
controls, whereas the number of early antral follicles was
decreased. In addition, in vivo Inh treatment caused an
increase in the percentage of apoptotic cells in
preantral, and early antral follicles. These results
suggest that inhibin produced by the dominant follicle may
act as a paracrine factor inhibiting the growth of
neighboring follicles; thus participating in the mechanism
of follicular selection.
Key words:
Apoptosis •
Follicle •
Granulosa cells •
Inhibin
